Enzalutamide Plus Metformin Versus Enzalutamide Alone in Metastatic Castration-resistant Prostate Cancer: A...

Area of Science:

• Oncology
• Pharmacology
• Metabolic Syndrome

Background:

• Metastatic castration-resistant prostate cancer (mCRPC) remains a significant clinical challenge.
• Standard treatments like enzalutamide have limitations, necessitating novel therapeutic strategies.
• Metformin, a diabetes drug, has shown potential anti-cancer properties in preclinical studies.

Purpose of the Study:

• To evaluate the efficacy of adding metformin to enzalutamide in patients with mCRPC.
• To assess the impact of metformin on disease control rate (DCR), event-free survival (EFS), and overall survival (OS).
• To explore the role of PTEN expression and body mass index (BMI) as predictive factors.

Main Methods:

• A randomized trial involving 166 patients with mCRPC from 2016-2021.
• Patients received either enzalutamide plus metformin or enzalutamide alone, stratified by BMI.
• Primary endpoint was DCR at 15 months; secondary endpoints included EFS, time to progression, and OS.

Main Results:

• Enzalutamide plus metformin did not significantly improve DCR or secondary endpoints compared to enzalutamide alone (DCR 52% vs 56%, p=0.64).
• Post hoc analysis indicated potential improvement in time to prostate-specific antigen progression (TTPSAP) with metformin in PTEN-expressing tumors (p=0.0074).
• Overweight/obese patients (BMI ≥25 kg/m²) demonstrated improved outcomes regardless of treatment arm (p < 0.009).

Conclusions:

• Addition of metformin to enzalutamide did not enhance outcomes in the overall mCRPC cohort.
• PTEN expression may serve as a predictive biomarker for metformin response.
• The 'obesity paradox' in prostate cancer warrants further investigation.